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F O R P H Y S I C I A N S – resources
Selective Estrogen Receptor Modulators
Tamoxifen
Tamoxifen was synthesized and developed in the 1960's and first reported as a treatment for advanced breast cancer in the early 1970's (13, 14). Currently, tamoxifen is being used in patients with invasive tumors, as well as for adjuvant therapy to surgery, radiation and chemotherapy in earlier disease stages. In the adjuvant therapy of breast cancer, studies show that overall (25%) and disease-free (45%) survival is significantly improved versus no adjuvant therapy (15). Recently, 20 mg of tamoxifen daily was shown to decrease the incidence of breast cancer by 45% in women at high risk compared to placebo-treated controls (16). The optimum duration of therapy remains to be determined, however, tamoxifen is currently recommended for at least 5 years (17).
While primarily an estrogen antagonist, tamoxifen displays agonist properties in the skeleton, uterus and cardiovascular system. Women receiving adjuvant tamoxifen therapy for breast cancer were found to have reductions in total cholesterol, low density lipoprotein-cholesterol (LDL-C) and lipoprotein(a) while high density lipoprotein (HDL-C) and triglycerides were essentially unchanged (18). These findings were similar to results in studies using tamoxifen in healthy postmenopausal women (19). In addition, tamoxifen was found to preserve lumbar spine and femur neck bone mineral density (BMD) in postmenopausal breast cancer patients.
Overall, tamoxifen is well tolerated by patients. Side effects more commonly encountered with tamoxifen include hot flushes, nausea and vaginal dryness. Unfortunately, tamoxifen is also associated with an increased risk of endometrial cancer by as much as 6-fold over placebo (17). Tamoxifen stimulates proliferation of the endometrium increasing the risk of endometrial polyps (25%), hyperplasia (50%) and cancer (6%). The majority of studies do not show a higher histopathologic grade or worse prognosis than those of other breast cancer patients not treated with tamoxifen (19, 20).
Tamoxifen also increases the risk of thromboembolic events such as deep venous thrombosis and pulmonary embolism (21). The incidence of thromboembolism was 0.9 percent for tamoxifen treated patients compared with 0.2 percent for placebo-treated patients. The increased risk of thromboembolic disease has not been elucidated but may be similar to that of estrogen. Because of the risks of endometrial cancer and thromboembolic events tamoxifen use is restricted to women with breast cancer or those in high-risk groups.
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